The aim of this study was to investigate the feasibility of intramyocardium kinetics of histamine release by microdialysis in the isolated rat heart and ascertain if the inhibition of histamine release is implicated in the antiarrhythmic effect of preconditioning. A 30 min normothermic global ischaemia model followed by 30 min reperfusion was carried out in the control group (n= 9). In the preconditioning group (n= 8) there was a 5 min global ischaemia followed by 10 min of reperfusion. A mast cell stabilizing group received the disodium cromoglycate ( 10 micro M, n= 10). The last group received a mast cell degranulator, compound 48/80 (1micro g ml (-1), n= 10). In the control group, the histamine release during reperfusion was significantly different from the basal concentration ( 18.4 +/- 6.5 vs 1.9 +/- 0.5 nM, P< 0.05) and was associated with a maximal period of severe arrhythmias. The ischaemic preconditioning modified the histamine release kinetics with an early mast cell degranulation ( 9.7 +/- 1.5 nM) and a significant decrease in the total period of severe arrhythmias in comparison with the control group ( P< 0.05). In the disodium cromoglycate group, the histamine release during reperfusion decreased ( 3.1 +/- 0.7 nM) and was associated with a maximal period of severe arrhythmias. In the C48/80 group, the increase in the histamine released during reperfusion ( 21.2 +/- 5.0 nM) was associated with a maximal period of severe arrhythmias. These results showed firstly the feasibility of kinetic histamine release in myocardium interstitial fluid on the isolated rat heart and secondly that the inhibition of histamine release did not play a direct role in the antiarrhythmic effect of preconditioning.